Protein Aggregation in the Aging Heart

As noted in this open access paper, protein misfolding and aggregation is a body-wide feature of aging, not only associated with the brain and neurodegenerative conditions. In the case of the heart, it is becoming apparent that misfolding of transthyretin to form amyloid can play a role in heart disease, and this form of amyloidosis may grow to be the majority cause of death for supercentenarians. The paper here is a more general tour of relevant mechanisms rather than a focus on any one specific protein, but is nonetheless interesting.

Protein homeostasis, the balance between protein synthesis and degradation, requires the clearance of misfolded and aggregated proteins and is therefore considered to be an essential aspect of establishing a physiologically effective proteome. Aging alters this balance, termed "proteostasis", resulting in the progressive accumulation of misfolded and aggregated proteins. Defective proteostasis leads to the functional deterioration of diverse regulatory processes during aging and is implicated in the etiology of multiple pathological conditions underlying a variety of neurodegenerative diseases and in age-dependent cardiovascular disease.

Detergent-insoluble protein aggregates have been reported by us in both aged and hypertensive hearts. The protein constituents were found to overlap with protein aggregates seen in neurodegenerative diseases such as Alzheimer's disease. Therefore, targeting these protein components of aggregates may be a promising therapeutic strategy for cardiovascular pathologies associated with aging, ischemia, and/or hypertension.